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Abstract
We modeled the expression of proteins in baseline bronchoalveolar lavage (BAL) samples from asymptomatic 60-year-old lifelong current smokers or healthy never-smokers, who were reevaluated after 6 to 7 years to record clinical outcome. Applying a technology toolbox consisting of replicate 2-dimensional gel separations, image annotation, and mass spectrometry identification, we catalogued a global set of proteins that were differentially expressed in individuals by presence, absence, and intensity scores. By use of multivariate analysis, we selected a subset of proteins that accurately separated smokers from never-smokers based on composite scoring. Follow-up after 6 to 7 years identified a group of individuals who had progressed to chronic obstructive pulmonary disease (COPD), Global Initiative for Chronic Obstructive Lung Disease stage 2. The baseline BAL samples of these eventual COPD patients shared a distinct protein expression profile that could be identified using partial least-squares discriminant analysis. This pattern was not observed in BAL samples of asymptomatic smokers free of COPD at 6- to 7-year follow-up. Our model suggests that certain patterns of protein expression occurring in the airways of long-term smokers may be detected in smokers susceptible to a progression of COPD disease, before disease is clinically evident.
Highlights
We modeled the expression of proteins in baseline bronchoalveolar lavage (BAL) samples from asymptomatic 60-year-old lifelong current smokers or healthy never-smokers, who were reevaluated after 6 to 7 years to record clinical outcome
In a recent study of BAL using liquid chromatography coupled with on-line linear ion trap quadrupole mass spectrometry (MS), we identified 481 high-to-low abundant proteins (6 )
Total lung capacity values did not differ significantly between smokers and never-smokers (Fig. 1); there was a trend for decreased lung function values in both the light and heavy smokers according to forced expiratory volume in 1 s (FEV1) and carbon monoxide lung diffusion capacity (DLCO)
Summary
We modeled the expression of proteins in baseline bronchoalveolar lavage (BAL) samples from asymptomatic 60-year-old lifelong current smokers or healthy never-smokers, who were reevaluated after 6 to 7 years to record clinical outcome. The baseline BAL samples of these eventual COPD patients shared a distinct protein expression profile that could be identified using partial least-squares discriminant analysis This pattern was not observed in BAL samples of asymptomatic smokers free of COPD at 6- to 7-year follow-up. 2-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and liquid chromatography platforms have been used to study clinical samples including bronchoalveolar lavage (BAL), nasal lavage, and whole lung tissue (3– 6 ). These studies have shown that smokers typically show increased concentrations of inflammatory and redox proteins, as well as decreases in surfactants and Clara cell secretory proteins, compared with nonsmokers.
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